Adenovirus-mediated wild-type p53 overexpression inhibits endothelial cell differentiation in vitro and angiogenesis in vivo

T. Riccioni, C. Cirielli, X. Wang, A. Passaniti, M. C. Capogrossi

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Gene therapy with the tumor suppressor gene p53 induces cancer cell apoptosis in vitro and in vivo and inhibits tumor growth in nude mice. We hypothesized that, in addition to cancer cell apoptosis, a replication-deficient adenovirus vector which carries the cDNA for human wild-type p53 (AdCMV.p53) may also modulate endothelial vein function and inhibit angiogenesis. Human umbilical vein endothelial cells (HUVEC) were infected at different multiplicities of infection (MOI) with either AdCMV.p53, the control vector AdCMV.null or were not infected. Western blot analysis showed p53 overexpression up to 7 days after infection with AdCMV.p53. HUVEC proliferation was either not affected (20 and 50 MOI) or inhibited to comparable levels (100 MOI; P <0.05) in AdCMV.p53- and AdCMV.null-infected versus uninfected cells. HUVEC differentiation into capillary-like structures on reconstituted basement membrane proteins (Matrigel) was assessed 48 h after infection (100 MOI). After 18 h on Matrigel the capillary-like network formed by AdCMV.p53-infected HUVEC was less extensive than that formed by both AdCMV.null-infected and uninfected control cells (P <0.05 versus either control). In contrast, conditioned medium from AdCMV.p53-infected HUVEC did not modulate endothelial cell differentiation on Matrigel. The effect of AdCMV.p53 on angiogenesis in vivo was assessed by injecting this vector subcutaneously in mice; 3 days later Matrigel containing basic fibroblast growth factor (bFGF) was injected at the same site. In other experiments AdCMV.p53 was injected simultaneously with an Ad vector coding for vascular endothelial growth factor (AdCMV.VEGF165) into the rate perirenal fat tissue. AdCMV.p53 significantly inhibited neovascularization induced by bFGF within the Matrigel plugs (P <0.05) or by AdCMV.VEGF165 in the fat tissue (P <0.05). Thus, the anti-angiogenic effect of Ad-mediated wild-type p53 overexpression may contribute to the ability of this viral vector to inhibit tumor growth.

Original languageEnglish
Pages (from-to)747-754
Number of pages8
JournalGene Therapy
Volume5
Issue number6
Publication statusPublished - 1998

Fingerprint

Adenoviridae
Human Umbilical Vein Endothelial Cells
Cell Differentiation
Endothelial Cells
Infection
Fibroblast Growth Factor 2
Neoplasms
Fats
Apoptosis
Conditioned Culture Medium
Growth
Tumor Suppressor Genes
Basement Membrane
Nude Mice
Genetic Therapy
Vascular Endothelial Growth Factor A
In Vitro Techniques
Veins
Membrane Proteins
Complementary DNA

Keywords

  • Adenovirus
  • Angiogenesis
  • Endothelium
  • Gene therapy
  • p53

ASJC Scopus subject areas

  • Genetics

Cite this

Riccioni, T., Cirielli, C., Wang, X., Passaniti, A., & Capogrossi, M. C. (1998). Adenovirus-mediated wild-type p53 overexpression inhibits endothelial cell differentiation in vitro and angiogenesis in vivo. Gene Therapy, 5(6), 747-754.

Adenovirus-mediated wild-type p53 overexpression inhibits endothelial cell differentiation in vitro and angiogenesis in vivo. / Riccioni, T.; Cirielli, C.; Wang, X.; Passaniti, A.; Capogrossi, M. C.

In: Gene Therapy, Vol. 5, No. 6, 1998, p. 747-754.

Research output: Contribution to journalArticle

Riccioni, T, Cirielli, C, Wang, X, Passaniti, A & Capogrossi, MC 1998, 'Adenovirus-mediated wild-type p53 overexpression inhibits endothelial cell differentiation in vitro and angiogenesis in vivo', Gene Therapy, vol. 5, no. 6, pp. 747-754.
Riccioni, T. ; Cirielli, C. ; Wang, X. ; Passaniti, A. ; Capogrossi, M. C. / Adenovirus-mediated wild-type p53 overexpression inhibits endothelial cell differentiation in vitro and angiogenesis in vivo. In: Gene Therapy. 1998 ; Vol. 5, No. 6. pp. 747-754.
@article{24754d3b4a5d4f1cbcf22f2bacb102df,
title = "Adenovirus-mediated wild-type p53 overexpression inhibits endothelial cell differentiation in vitro and angiogenesis in vivo",
abstract = "Gene therapy with the tumor suppressor gene p53 induces cancer cell apoptosis in vitro and in vivo and inhibits tumor growth in nude mice. We hypothesized that, in addition to cancer cell apoptosis, a replication-deficient adenovirus vector which carries the cDNA for human wild-type p53 (AdCMV.p53) may also modulate endothelial vein function and inhibit angiogenesis. Human umbilical vein endothelial cells (HUVEC) were infected at different multiplicities of infection (MOI) with either AdCMV.p53, the control vector AdCMV.null or were not infected. Western blot analysis showed p53 overexpression up to 7 days after infection with AdCMV.p53. HUVEC proliferation was either not affected (20 and 50 MOI) or inhibited to comparable levels (100 MOI; P <0.05) in AdCMV.p53- and AdCMV.null-infected versus uninfected cells. HUVEC differentiation into capillary-like structures on reconstituted basement membrane proteins (Matrigel) was assessed 48 h after infection (100 MOI). After 18 h on Matrigel the capillary-like network formed by AdCMV.p53-infected HUVEC was less extensive than that formed by both AdCMV.null-infected and uninfected control cells (P <0.05 versus either control). In contrast, conditioned medium from AdCMV.p53-infected HUVEC did not modulate endothelial cell differentiation on Matrigel. The effect of AdCMV.p53 on angiogenesis in vivo was assessed by injecting this vector subcutaneously in mice; 3 days later Matrigel containing basic fibroblast growth factor (bFGF) was injected at the same site. In other experiments AdCMV.p53 was injected simultaneously with an Ad vector coding for vascular endothelial growth factor (AdCMV.VEGF165) into the rate perirenal fat tissue. AdCMV.p53 significantly inhibited neovascularization induced by bFGF within the Matrigel plugs (P <0.05) or by AdCMV.VEGF165 in the fat tissue (P <0.05). Thus, the anti-angiogenic effect of Ad-mediated wild-type p53 overexpression may contribute to the ability of this viral vector to inhibit tumor growth.",
keywords = "Adenovirus, Angiogenesis, Endothelium, Gene therapy, p53",
author = "T. Riccioni and C. Cirielli and X. Wang and A. Passaniti and Capogrossi, {M. C.}",
year = "1998",
language = "English",
volume = "5",
pages = "747--754",
journal = "Gene Therapy",
issn = "0969-7128",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Adenovirus-mediated wild-type p53 overexpression inhibits endothelial cell differentiation in vitro and angiogenesis in vivo

AU - Riccioni, T.

AU - Cirielli, C.

AU - Wang, X.

AU - Passaniti, A.

AU - Capogrossi, M. C.

PY - 1998

Y1 - 1998

N2 - Gene therapy with the tumor suppressor gene p53 induces cancer cell apoptosis in vitro and in vivo and inhibits tumor growth in nude mice. We hypothesized that, in addition to cancer cell apoptosis, a replication-deficient adenovirus vector which carries the cDNA for human wild-type p53 (AdCMV.p53) may also modulate endothelial vein function and inhibit angiogenesis. Human umbilical vein endothelial cells (HUVEC) were infected at different multiplicities of infection (MOI) with either AdCMV.p53, the control vector AdCMV.null or were not infected. Western blot analysis showed p53 overexpression up to 7 days after infection with AdCMV.p53. HUVEC proliferation was either not affected (20 and 50 MOI) or inhibited to comparable levels (100 MOI; P <0.05) in AdCMV.p53- and AdCMV.null-infected versus uninfected cells. HUVEC differentiation into capillary-like structures on reconstituted basement membrane proteins (Matrigel) was assessed 48 h after infection (100 MOI). After 18 h on Matrigel the capillary-like network formed by AdCMV.p53-infected HUVEC was less extensive than that formed by both AdCMV.null-infected and uninfected control cells (P <0.05 versus either control). In contrast, conditioned medium from AdCMV.p53-infected HUVEC did not modulate endothelial cell differentiation on Matrigel. The effect of AdCMV.p53 on angiogenesis in vivo was assessed by injecting this vector subcutaneously in mice; 3 days later Matrigel containing basic fibroblast growth factor (bFGF) was injected at the same site. In other experiments AdCMV.p53 was injected simultaneously with an Ad vector coding for vascular endothelial growth factor (AdCMV.VEGF165) into the rate perirenal fat tissue. AdCMV.p53 significantly inhibited neovascularization induced by bFGF within the Matrigel plugs (P <0.05) or by AdCMV.VEGF165 in the fat tissue (P <0.05). Thus, the anti-angiogenic effect of Ad-mediated wild-type p53 overexpression may contribute to the ability of this viral vector to inhibit tumor growth.

AB - Gene therapy with the tumor suppressor gene p53 induces cancer cell apoptosis in vitro and in vivo and inhibits tumor growth in nude mice. We hypothesized that, in addition to cancer cell apoptosis, a replication-deficient adenovirus vector which carries the cDNA for human wild-type p53 (AdCMV.p53) may also modulate endothelial vein function and inhibit angiogenesis. Human umbilical vein endothelial cells (HUVEC) were infected at different multiplicities of infection (MOI) with either AdCMV.p53, the control vector AdCMV.null or were not infected. Western blot analysis showed p53 overexpression up to 7 days after infection with AdCMV.p53. HUVEC proliferation was either not affected (20 and 50 MOI) or inhibited to comparable levels (100 MOI; P <0.05) in AdCMV.p53- and AdCMV.null-infected versus uninfected cells. HUVEC differentiation into capillary-like structures on reconstituted basement membrane proteins (Matrigel) was assessed 48 h after infection (100 MOI). After 18 h on Matrigel the capillary-like network formed by AdCMV.p53-infected HUVEC was less extensive than that formed by both AdCMV.null-infected and uninfected control cells (P <0.05 versus either control). In contrast, conditioned medium from AdCMV.p53-infected HUVEC did not modulate endothelial cell differentiation on Matrigel. The effect of AdCMV.p53 on angiogenesis in vivo was assessed by injecting this vector subcutaneously in mice; 3 days later Matrigel containing basic fibroblast growth factor (bFGF) was injected at the same site. In other experiments AdCMV.p53 was injected simultaneously with an Ad vector coding for vascular endothelial growth factor (AdCMV.VEGF165) into the rate perirenal fat tissue. AdCMV.p53 significantly inhibited neovascularization induced by bFGF within the Matrigel plugs (P <0.05) or by AdCMV.VEGF165 in the fat tissue (P <0.05). Thus, the anti-angiogenic effect of Ad-mediated wild-type p53 overexpression may contribute to the ability of this viral vector to inhibit tumor growth.

KW - Adenovirus

KW - Angiogenesis

KW - Endothelium

KW - Gene therapy

KW - p53

UR - http://www.scopus.com/inward/record.url?scp=0031857875&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031857875&partnerID=8YFLogxK

M3 - Article

C2 - 9747454

AN - SCOPUS:0031857875

VL - 5

SP - 747

EP - 754

JO - Gene Therapy

JF - Gene Therapy

SN - 0969-7128

IS - 6

ER -